口腔鳞癌组织中angiopoietin-1、angiopoietin-2mrna表达及其临床意义

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1、中图分类号：R89；R36；R39硕士学位论文口腔鳞癌组织中Angiopoietin-1、Angiopoietin-2mRNA表达及其临床意义院（系）、所临床医学院研究生姓名梁博学科、专业肿瘤学导师姓名樊晋川教授二Ο一二年四月1目录1口腔鳞癌组织中Angiopoietin-1、Angiopoietin-2mRNA表达及其临床意义„„„„„„„„„„„„„„„„„„11.1中文摘要„„„„„„„„„„„„„„„„„„„„„11.2英文摘要„„„„„„„„„„„„„„„„„„„„„31.3前言„„„„„„„„„„„„„„„„„„„„„„

2、„51.4材料与方法„„„„„„„„„„„„„„„„„„„„91.5结果„„„„„„„„„„„„„„„„„„„„„„„161.6讨论„„„„„„„„„„„„„„„„„„„„„„„201.7结论„„„„„„„„„„„„„„„„„„„„„„„311.8参考文献„„„„„„„„„„„„„„„„„„„„„321.9英汉缩略词对照表„„„„„„„„„„„„„„„„„372致谢„„„„„„„„„„„„„„„„„„„„„„„383口腔鳞癌中Angiopoietin的表达及功能的研究进展（综述）„„„„„„„„„„„„„„„„„„„„„„„„„39

3、2口腔鳞癌组织中Angiopoietin-1、Angiopoietin-2mRNA表达及其临床意义摘要目的：检测口腔鳞癌（oralsquamouscellcarcinoma，OSCC）和口腔正常黏膜中促血管生成素-1（Ang-1）和促血管生成素-2（Ang-2）mRNA表达水平的差异，探讨Ang-1和Ang-2基因表达与临床病理学参数和肿瘤血管生成的关系。检测口腔鳞癌组织中促血管生成素-1（Ang-1）和促血管生成素-2（Ang-2）蛋白表达水平的差异，探讨在口腔鳞癌组织和正常口腔黏膜组织中蛋白表达的差异。检测口腔鳞癌组织中微血管密

4、度（MVD）,探讨MVD与口腔鳞癌病人临床病理学参数之间的关系。探讨在口腔鳞癌中促血管生成素-2（Ang-2）mRNA表达阴性组和阳性组之间的MVD的区别。方法：收集四川省肿瘤医院头颈外科手术切除送检标本50例。其中OSCC标本35例，正常口腔黏膜组织l5例，所有标本均经病理证实。在术中，于无菌条件下切取2块0.5cm×0.5cm组织，其一立即经液氮速冻后置于液氮罐中保存备用，另一块置于10％甲醛溶液中固定，供病理检查及免疫组化使用。采用半定量RT-PCR检测正常人口腔黏膜组织15例和OSCC标本35例的Ang-1及Ang-2mRN

5、A表达水平；采用常规免疫组化检测所有标本中Ang-1及Ang-2的蛋白表达；免疫组化检测口腔鳞癌标本中CD34表达并计数微血管密度。结果：Ang-2mRNA在OSCC组织和正常黏膜组织中均有表达，OSCC组织中Ang-2mRNA的表达显著高于正常黏膜组织（P<0.01），与黏膜下层浸润OSCC组织及正常黏膜组织比较，肌层浸润的OSCC组织中黏膜下层浸润16例，Ang-2mRNA阳性6例，阴性10例，肌层浸润19例，1Ang-2mRNA阳性14例，阴性5例。Ang-2表达差异有统计学意义（P＜0.05）；Ang-1在OSCC组织和正常

6、黏膜中表达均较弱或呈阴性，二者比较无统计学意义（P>0.05）。Ang-1/Ang-2阳性染色定位于血管内皮细胞的胞浆及胞膜，呈棕黄色。口腔鳞癌中的Ang-1蛋白表达明显下调而Ang-2蛋白明显上调。Ang-1在口腔鳞癌组织与正常口腔黏膜组织比较有显著性差异（P＜0.05）。Ang-2在口腔鳞癌组织与正常口腔黏膜组织比较也有显著性差异（P＜0.05）。Ang-2阳性表达的OSCC组织中MVD均值为48.10，阴性表达的OSCC组织中MVD均值为38.14，后者显著低于前者(t＝6.871，P＜0.05)。说明OSCC中Ang-2mR

7、NA的表达与MVD呈正相关。口腔鳞癌组织中微血管密度与口腔鳞癌病人年龄，性别，病理分级，临床分期，淋巴结转移之间分析，未见统计学差异（P＞0.05）。结论：Ang-1蛋白在正常口腔黏膜组织的表达高于口腔鳞癌组织；Ang-2蛋白在口腔鳞癌组织中的表达高于口腔正常黏膜组织；Ang-2mRNA在口腔鳞癌组织中的表达高于正常口腔黏膜；Ang-2的表达强度与口腔鳞癌的浸润深度有关，在肿瘤恶性进展中可能起到重要的作用。Ang-2的表达与口腔鳞癌的微血管密度有关，Ang-2参与了OSCC的血管生成。口腔鳞癌的微血管密度与淋巴结转移及临床分期无明显

8、相关性，这点需要更大样本量做进一步研证。关键词：口腔鳞癌；促血管生成素2；微血管密度；肿瘤血管生成2ExpressionandclinicalsignificanceofAngiopoietin-1andAngiopoietin-2i